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Male hypogonadism affects 10-30% of the male population and is often under-recognized and under-treated. Different replacement formulations exist, each with specific benefits and limitations. These replacements include gels, patches and short- and long-acting injectables. JATENZO® (oral testosterone undecanoate; Clarus Therapeutics Inc., Northbrook, IL, US) is the first oral formulation of testosterone approved by the US Food and Drug Administration. TLANDO® (oral testosterone undecanoate; Lipocine Inc., Salt Lake City, UT, US), another oral testosterone formulation, has also recently been approved by the US Food and Drug Administration. Based on unique chemistry using a self-emulsifying drug delivery system and lymphatic absorption, JATENZO and TLANDO address some of the limitations of other dosing routes while providing a safe option without evidence of liver dysfunction. This review discusses various testosterone treatment options, focusing on the role and pharmacokinetics of the new oral formulations., Competing Interests: Disclosure: Salman Z Bhat and Adrian S Dobs have no financial or non-financial relationships or activities to declare in relation to this article., (© Touch Medical Media 2022.)

A 54-year-old man had been drinking approximately 1.2 L of soy milk (equivalent to approximately 310 mg of isoflavones) per day for the previous 3 years. He then developed erectile dysfunction and gynecomastia. On an examination in our department in May, blood tests showed low gonadotropin and testosterone levels, indicative of secondary hypogonadism. He stopped drinking soy milk on his own in June of that year. When he was admitted in August, blood tests showed an improved gonadal function. Secondary hypogonadism caused by the excessive intake of isoflavones in soy milk was diagnosed. In men, an excessive intake of isoflavones may cause feminization and secondary hypogonadism.

Androgen deficiency is a common medical conditions that affects males of all ages. Transplantation of testosterone-producing cells is a promising treatment for male hypogonadism. However, getting a cell source with the characteristics of Leydig cells (LCs) is still a challenge. Here, a high-efficiency reprogramming of skin-derived fibroblasts into functional Leydig-like cells (LLCs) based on epigenetic mechanism was described. By performing an integrated analysis of genome-wide DNA methylation and transcriptome profiling in LCs and fibroblasts, the potentially epigenetic-regulating steroidogenic genes and signaling pathways were identified. Then by using CRISPR/dCas9 activation system and signaling pathway regulators, the male- or female-derived fibroblasts were reprogrammed into LLCs with main LC-specific traits. Transcriptomic analysis further indicated that the correlation coefficients of global genes and transcription factors between LLCs and LCs were higher than 0.81 and 0.96, respectively. After transplantation in the testes of hypogonadal rodent models, LLCs increased serum testosterone concentration significantly. In type 2 diabetic rats model, LLCs which were transplanted in armpit, have the capability to restore the serum testosterone level and improve the hyperglycemia status. In conclusion, our approach enables skin-derived fibroblasts reprogramming into LLCs with high fidelity, providing a potential cell source for the therapeutics of male hypogonadism and metabolic-related comorbidities., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

Introduction It is controversial whether or not testing the length of the androgen receptor polymorphism in clinical practice is useful for correct diagnosis and treatment of hypogonadism. Aim To describe the molecular and clinical implications of testing the length of the androgen receptor polymorphism for treatment of hypogonadism in both male and female subjects. Methods A systematic Medline search was conducted using several terms related to and including the terms 'androgen receptor,' ' CAG-repeat polymorphism,' 'male hypogonadism,' 'female hypogonadism,' and 'neurodegenerative disease.' Main Outcome Measures Clinical evidence that demonstrates the importance of CAG repeat number investigation in male and female hypogonadism. Results A thorough review of the clinical utility of CAG repeat polymorphism investigation in men and women with hypogonadism is presented. Conclusions The role of AR CAG repeat number investigation in hypogonadism (male and female) is not yet established in the clinical practice. In both sexes, a role during clinical management of hormonal replacement therapies may be hypothesized, but the CAG repeat number's relationship with the presence or absence of hypogonadal symptoms remains unclear. Pharmacogenomic investigations of the AR polymorphism may be a future option to tailor testosterone titration individually and to better identify subjects as potentially more or less responsive to treatments; also, investigation may be important to individually predict beneficial and side effects in special subpopulations, specifically, obese men and postmenopausal women. Francomano D, Greco EA, Lenzi A, and Aversa A. CAG repeat testing of androgen receptor polymorphism: Is this necessary for the best clinical management of hypogonadism? J Sex Med 2013;10:2373-2381. [ABSTRACT FROM AUTHOR]

Male hypogonadism is a condition in which the body does not produce enough testosterone, resulting in symptoms such as depressed mood, decreased sex drive, decreased skeletal muscle, and increased fat mass. Male hypogonadism can be readily treated with many available treatments when clinically indicated. The advent of readily available testosterone therapy has increased the importance of finding the most efficacious and cost-efficient treatment modality to approach these patients. Testosterone is typically administered through intramuscular or subcutaneous injections, topical gels, and oral tablets. The efficacy of testosterone therapy on hypogonadal men has been widely studied. However, there has been little research done comparing each modality against each other. This paper seeks to compare the various modalities of testosterone replacement therapy using various parameters such as the beneficial effects on bone mineral density, skeletal muscle mass, fat mass, and libido while simultaneously weighing the distinct undesirable side effects of each form of administration. Our investigation analyzes the methodology and results of the existing research within this field. It aims to draw a nuanced conclusion about the current standard of care for testosterone replacement therapy. According to our research and statistical analyses, we have concluded that oral administration has shown to be as advantageous as other modalities for male hypogonadism. Currently, injectables are the modality of choice, but with the right improvements, oral administration can potentially overtake injectables and transdermal testosterone as the treatment of choice., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ahmad et al.)

Eur J Clin Invest 2012; 42 (11): 1205-1212 Abstract Background The effect of male hypogonadism on the immune response is poorly understood, even though testosterone has both immunosuppressive and anti-inflammatory effects in men. Design In this study, we compared the distribution and functional status of peripheral blood (PB) monocytes, dendritic cells (DCs) [CD16+ (monocytoid), CD33+ (myeloid) and CD33− (plasmacytoid)] and CD4+ CD25+ CD127−/lo regulatory T cells from hypogonadic men and control subjects. Immunophenotypic studies were performed both on resting and in vitro-stimulated cells. Results Overall, no significant differences were detected on the number of monocytes, DCs and CD4+ CD25+ CD127−/lo regulatory T cells between both groups of subjects. However, hypogonadic men showed slightly higher numbers of circulating CD16+ cells expressing the CD107b activation/degranulation-associated marker than controls, such differences reaching statistical significance after in vitro stimulation with CpG oligodeoxynucleotides. Interestingly, antigen-stimulated expression of CD107b on CD16+ cells inversely correlated with the serum concentrations of total testosterone ( r2 = −0·45; P = 0·01), free testosterone ( r2 = −0·48; P = 0·005), calculated free testosterone ( r2 = −0·44; P = 0·01) and bioavailable testosterone ( r2 = −0·46; P = 0·008) among all cases studied, as well as with both the LH ( r2 = −0·53, P = 0·04) and FSH ( r2 = −0·54, P = 0·04) serum levels among hypogonadic men. Conclusions These findings show an enhanced immunological response of circulating (activated) CD16+ DCs to antigen stimulation, which was inversely related to testosterone and gonadotropin serum levels. Such findings suggest a modulation by the hypothalamic-hypophyseal-gonadal axis of the immune response and may have clinical implications for hypogonadic men, as regards susceptibility to autoimmune diseases and increased responses to antigenic stimuli. [ABSTRACT FROM AUTHOR]

The pathogenesis of benign prostatic hyperplasia-lower urinary tract symptoms (BPH-LUTS) is complicated, multifactorial, and incompletely understood. A number of recent observations have provided for new insights and offer a better appreciation for, and the understanding of, the pathophysiological and hormonal contributions for the development and progression of prostatic enlargement. A major paradox has been the progressive increase in the prostate size at a time when the peripheral blood testosterone levels are decreasing as men age. This has been associated with the findings of increasing obesity-related states and the manifestation of BPH-LUTS. Several converging and new findings combine the mechanisms that result in an integration of the hypogonadal-obesity-increased intra-abdominal pressure (IAP)-BPH-LUTS connection. The net positive caloric balance results increased the IAP and damaged the one-way valves of the internal spermatic veins. This results in an increased venous back pressure that leads to the reflux of the high testicular testosterone concentrations and venous pressures that are transmitted to the communicating prostatic venous system. Simultaneously, increasing obesity results in an increased aromatase activity, which leads to a reduction of the testosterone levels. Consequently, there is also an increased estradiol production, which inhibits gonadotropin secretion and the production of testosterone. This hypogonadal obesity cycle eventually results in a progressive hypogonadal state, while the prostate continues to enlarge and produce increasing LUTS. [ABSTRACT FROM AUTHOR]

Background. In the general population, accumulating data support a link between low testosterone levels and mortality by all causes, but especially by cardiovascular disease (CVD). Also, accelerated arterial stiffness has been recognized as an important cardiovascular risk factor. Here, we explored the association between testosterone levels and risk of death in male haemodialysis (HD) patients, whose arterial system is characterized by generalized stiffening.Methods. In this three-centre prospective observational study, 111 male HD patients after completion of baseline assessment, including measurement of male sex hormones and pulse wave velocity (PWV), were followed up for CVD and all-cause mortality.Results. Of the 111 patients studied, 54 were found with and 57 without testosterone deficiency, defined as testosterone levels <8 nmol/L. During a median follow-up period of 37 months, 49 deaths occurred, 28 (57%) of which were caused by CVD. Testosterone deficiency patients had increased CVD and all-cause mortality {crude hazard ratio: 3.14 [95% confidence interval (CI), 1.21–8.16] and 3.09 (95% CI, 1.53–6.25), respectively}, even after adjustment for age, body mass index, serum albumin and C-reactive protein, prevalent CVD and HD vintage. The association of testosterone with CVD mortality, but not with all-cause mortality, was lost after adjusting for PWV, an index of arterial stiffness. Testosterone levels were inversely related to PWV (r = −0.441; P < 0.001).Conclusion. We showed that testosterone deficiency in male HD patients is associated with increased CVD and all-cause mortality and that increased arterial stiffness may be a possible mechanism explaining this association. [ABSTRACT FROM PUBLISHER]

Objectives: To investigate the effects of senescence on testicular volume and metabolism by quantitative analysis of volumetric and functional data provided by genital ultrasonography (US) and 2-deoxy-2-[(18)F]fluoro-D-glucose(-)positron emission tomography (FDG-PET), respectively.Methods: Three hundred twenty (PET 173, US 147) male subjects (average age, 47.9 ± 24.1 years; range, 11-90 years) who previously underwent US or FDG-PET imaging were included in this retrospective study. Testicular volumes and FDG maximum standardized uptake values (SUV(max)) were correlated with age using polynomial regression and Pearson linear regression analysis.Results: With cross-sectional analysis, the best-fit curves demonstrated statistically significant overall correlations between changes in both the volume and metabolism (SUV(max)) of the testicle and increasing age (volume: R(2) = 0.42, p = 0.0002; SUV(max): R(2) = 0.26, p < 0.0001). Testicular volume rapidly increases during puberty and peaks at age 30 years. Subsequently, the volume of the testes stabilizes in a plateau-like manner until age 60 years. After age 60 years, this study shows that testicular volume decreases significantly. Testicular glucose metabolism increases until age 40 years, after which it declines gradually over time at a constant rate.Conclusion: Testicular volume and metabolism appear to be significantly affected by advancing age at different rates during the different stages of lifespan. The rapid increase in testicular volume and metabolism parallel the onset and progression of puberty and positively correlate with increasing age up to ages 30-40 years. Between ages 40 and 60 years, testicular volume and metabolism remain relatively constant with only a minimal decline. After age of 60 years, the testicular volume significantly declines, while testicular metabolism progressively declines until age 90 years. [ABSTRACT FROM AUTHOR]

Male hypogonadism is a condition characterized by inadequate testicular production of sex steroids and sperms; however, the term is more commonly used to identify testosterone (T) deficiency. When fertility is not desired, T replacement therapy (TRT) is the gold standard. To review the pathogenesis of male hypogonadism and the available preparations for TRT, along with the main clinical outcomes. A systematic search of published evidence was performed using Medline (1969 to September 2010). Data from a consecutive series of subjects attending our Andrology Unit were also provided to stress the clinical correlates of low T. Inventories available for detecting hypogonadism (including ANDROTEST) were overviewed. The most important studies regarding the pathogenesis of male hypogonadism and the preparations for its treatment were reviewed. To review TRT outcomes, only meta-analytic studies were considered. The goals of TRT are to alleviate clinical symptoms and to restore serum T levels to the mid-normal range, without significant side effects or safety concerns. Different T formulations have been approved. TRT is associated with a reduction of fat mass, an increase of lean mass, and a possible positive effect on lipid profile and glycometabolic control. Bone density and depressive symptoms are improved by TRT, while effects on cardiovascular risk and frailty are more controversial. No increase of prostate cancer and prostate-related problems has been reported so far. TRT, alone or in combination with phosphodiesterase type 5 inhibitors, is considered the first-line therapy in hypogonadal subjects with erectile dysfunction. T deficiency is highly prevalent in the aging male and represents a sign of physical and sexual frailty. The significance of low T in elderly men has yet to be completely clarified. Large, prospective intervention trials will help solve this dilemma. [ABSTRACT FROM AUTHOR]

Abstract: This study has examined whether upregulation of endothelin receptor A, leptin and phosphorylated protein kinase Cɛ contributes to stress-induced testicular damaged and its possible reversal by endothelial (ET) antagonism. Adult male Sprague–Dawley rats were randomly divided into control and isoproterenol (ISO 1mg/kg, subcutaneous (s.c.), 10 days) groups, and intervened with the ET receptor antagonist CPU0213 (20mg/kg, s.c.), on days 6–10. In ISO group, testicular succinate dehydrogenase, lactate dehydrogenase, acid phosphotase, and γ-glutamyl transpeptidase, and serum testosterone decreased, whereas FSH increased, relative to control. The seminiferous tubules were damaged in association with testicular upregulation of protein abundance of leptin and pPKCɛ, and mRNA and protein expression of leptin receptor (OBRb) and ETA. CPU0213 was effective in ameliorating these abnormalities. Over-expression of ETA and leptin accounting for the testis dysfunction is likely to be mediated by pPKCɛ in the ISO treated rats. The upregulated ET pathway appears to be critical in pathologies of the testis. [Copyright &y& Elsevier]

Abstract: Accurate measurement of testosterone concentration is of critical importance when diagnosing and treating male hypogonadism, congenital adrenal hyperplasia, premature or delayed puberty, and androgen excess in polycystic ovary syndrome or other virilizing conditions. However, some assays have inherent limitations and biases that affect measurement of low-testosterone values. Therefore, we developed a highly specific online mass spectrometry method. Sera were extracted online using high-turbulence flow liquid chromatography coupled to analytical HPLC and atmospheric pressure chemical ionization tandem mass spectrometry (HTLC–APCI-MS/MS). Analyte ions were monitored by multiple reaction monitoring (MRM). Total analysis time was 1.15min per sample when using the multiplexing system. Testosterone concentrations were measured directly from 150μL of serum or plasma without derivatization or liquid–liquid extraction. The lower limit of quantification was 0.3ng/dL, and the assay was linear up to 2000ng/dL. The method compared very well with an established RIA: y =1.02x +1.5, r 2 =0.994. Comparison with a platform immunoassay confirmed the previously reported ICMA positive bias at low concentrations. Male and female adult and pediatric reference ranges were developed for this very sensitive and accurate high-throughput LC–MS/MS method. This method is suitable for measuring the expected low-testosterone concentrations seen in women, children, and hypogonadal males and for monitoring testosterone suppressive therapy in prostate cancer patients. [Copyright &y& Elsevier]

Abstract: A reduced concentration of serum testosterone resulting in male hypogonadism is a well described endocrine abnormality associated with classical signs and symptoms. This manuscript presents one such patient. However, low serum testosterone is being recognized more commonly associated with aging and chronic disease. It is in this situation in which the signs and symptoms of male hypogonadism can be subtle and non-specific. This manuscript reviews examples of such situations and highlights our need to have a reliable and accurate measure of serum testosterone. Both clinicians and researchers need better assays to better understand basic mechanisms, diagnose, treat, and monitor men with testosterone deficiency. [Copyright &y& Elsevier]

The article focuses on morphological and finite element analyses, μmagnetic resonance imaging, and the effect of testosterone treatment on the tibial bone in eugonadal and hypodonadal men. Topics include trabecular structure, bone mass density, imaging of the distal tibia, compression and shear tests, calculation of the anisotropic stiffness tensor, and digital topological analysis.

Introduction. Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are characterized by insulin resistance and often associated with male hypogonadism. Aim. To discriminate the specific contribution of T2DM and MetS to male hypogonadism. Methods. A consecutive series of 1,134 (mean age 52.1 ± 13 years) male patients with sexual dysfunction was studied. Main Outcome Measures. Several hormonal and biochemical parameters were studied along with ANDROTEST, a 12-item validated structured interview, specifically designed for the screening of hypogonadism (total testosterone [TT] <10.4 nmol/L or free testosterone [FT] <37 pmol/L) in a male population with sexual dysfunction. Results. Irrespective of the criteria used to define hypogonadism, MetS was associated with a significantly higher prevalence of the condition, both in subjects with and without T2DM (41% and 29% vs. 13.2% and 77.1% and 58% vs. 40.6%, respectively, for TT and FT in patients with MetS and with or without T2DM, when compared with subjects without MetS and T2DM; both P < 0.0001). Conversely, T2DM was associated with a higher prevalence of hypogonadism in subjects with MetS but not in those without MetS. Patients with MetS, with or without T2DM, also showed a higher ANDROTEST score when compared with patients without MetS. Logistic multivariate regression analysis, incorporating the five components of MetS, identified a significant association of elevated waist circumference and hypertriglyceridemia with hypogonadism both in patients, with or without T2DM. Conclusions. Our study demonstrated that MetS, and in particular visceral adiposity (as assessed by increased waistline and hypertriglyceridemia), is specifically associated with hypogonadism in subjects consulting for sexual dysfunction. Corona G, Mannucci E, Petrone L, Balercia G, Paggi F, Fisher AD, Lotti F, Chiarini V, Fedele D, Forti G, and Maggi M. GNCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction. J Sex Med 2007;4:1038–1045. [ABSTRACT FROM AUTHOR]

Differences in endothelin-1 (ET-1) blood plasma levels were established between healthy men and women. Little is known about vascular effects of testosterone and the interactions between sex hormones and endothelin. In order to study the relationship between ET-1 and testosterone in more detail, we have investigated 33 male patients with various forms of hypogonadism (13 with hypergonadotropic hypogonadism and 20 with hypogonadotropic hypogonadism). Fourteen age-matched healthy males served as controls. The basal ET-1 levels in patients with hypogonadism (0.96 ± 0.12 fmol/mL) (mean ± SEM) were significantly higher in comparison with the controls (0.44 ± 0.04 fmol/mL), p < 0.01. Fifteen individuals of these patients were studied during the therapy with testosterone depot 250 mg i.m. The ET-1 levels decreased in this group from 0.99 ± 0.22 to 0.78 ± 0.14 fmol/mL at the third and to 0.76 ± 0.25 fmol/mL at the sixth month of the medication, respectively. The differences were not significant compared with the initial levels, but the concentrations at the sixth month of the treatment were not statistically different in comparison with the ET-1 levels of the controls. There was no significant difference in lipid data between patients before and during testosterone medication, except for the high-density lipoprotein cholesterol, which decreased at the third month of the treatment. Our results show that plasma ET-1 levels in males with hypogonadism are elevated with a tendency to decrease after testosterone administration. The optimum testosterone is not associated with enhanced cardiovascular risk as far as ET-1 plasma levels and lipids are concerned. [ABSTRACT FROM AUTHOR]

Aim: To determine the involvement of apoptotic cell death in postnatal pathogenesis in mutant strain of hypogonadic ( hgn/hgn) rats testes. We evaluated the numbers and types of cells undergoing apoptotic cell death. Methods: Tissue sections were stained by the TUNEL method for in situ detection of apoptotic cells, with specific antibodies used as markers of testicular somatic and germ cells. Results: We found that apoptosis in the hgn/hgn testes during the early postnatal period occurred primarily in Sertoli cells, which should actively proliferate during this stage of differentiation. These findings strongly suggest that the normal allele of hgn is involved in the direct or indirect control of differentiation and proliferation of Sertoli cells. Conclusion: To our knowledge, this is the first report demonstrating early postnatal apoptosis of Sertoli cells, suggesting that the hgn/hgn rat is a unique model for the study of Sertoli cell deficiency. [ABSTRACT FROM AUTHOR]

Symptomatic late-onset hypogonadism is associated not only with a decline in serum testosterone, but also with a rise in serum estradiol. These endocrine changes negatively affect libido, sexual function, mood, behavior, lean body mass, and bone density. Currently, the most common treatment is exogenous testostosterone therapy. This treatment can be associated with skin irritation, gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts. In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone (T) and improving the testosterone/estrogen (T/E) ratio. Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospectively. Analysis of baseline and follow-up serum levels of testosterone and estradiol levels were performed. The mean age was 39 years, and the mean pretreatment testosterone and estrogen levels were 247.6 ± 39.8 ng/dL and 32.3 ± 10.9, respectively. By the first follow-up visit (4–6 weeks), the mean testosterone level rose to 610.0 ± 178.6 ng/dL ( P < 0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 ( P < 0.001). There were no side effects reported by the patients. Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estadiol ratio in men with hypogonadism. This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway. Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, and Goluboff E. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med **; **: **–**. [ABSTRACT FROM AUTHOR]

The pineal gland, through the rhythmic production of melatonin, seems to play an important role in the control of the reproductive function of many vertebrate species. In contrast, the effects of the pineal gland in humans and the relationship between gonadotropins and melatonin secretion are not yet clarified. On the basis of these considerations, the aim of the present study was to clarify whether melatonin serum concentrations were altered in males with different hypothalamo-pituitary–gonadal disturbances, in comparison to normal individuals. We have studied 36 individuals divided into three groups according to their gonadotropin status: normals, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. They were submitted to blood sample withdrawal at 03.00, 11.00 and 19.00 h for melatonin determination according to a radioimmunological method, without extraction of the sample. The results obtained in the present study suggest the existence of an interaction between the pituitary and the pineal gland. In fact, in the case of hypersecretion of gonadotropins, nocturnal melatonin release is reduced, while night melatonin secretion is increased in the opposite situation (hypogonadotropic hypogonadism). Both these endocrine pathologies are characterized by a reduced sexual steroid secretion; for that reason, this reduction cannot be regarded as responsible for the two opposite dysfunctions of melatonin release. In conclusion, our study shows that darkness-dependent release of melatonin in males with hypogonadotropic hypogonadism is significantly higher in comparison with the healthy men, while it is significantly reduced in patients with hypergonadotropic hypogonadism. A strong significant negative correlation is also found between gonadotropins and melatonin release. [ABSTRACT FROM AUTHOR]

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Background: No randomized study exists comparing the effects of different modes of androgen substitution on bone mineral density (BMD). Methods: We performed a prospective, randomized, trial assigning 53 hypogonadal men to the following treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was determined by peripheral quantitative computed tomography. Results: At baseline, men with secondary hypogonadism (n = 33) had a lower BMD (–1.52 ± 0.23 SDS; Z-scores) than men with primary hypogonadism (n = 20, –0.87 ± 0.23 SDS, p < 0.01). In men with primary hypogonadism, the BMD increased dose dependently (crystalline testosterone +7.0 ± 1.3%, testosterone enanthate +4.8 ± 0.2%, testosterone undecanoate +3.4 ± 2.5%, mesterolone +0.8 ± 1.6%) after 6 months of therapy. Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD. Conclusions: In primary hypogonadal men the BMD responds dose dependently to testosterone substitution, whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Monitoring bone density (BMD) in hypogonadal and testosterone (T) substituted men is a major component of andrological therapy and is performed by methods that are cost-intensive and use radiation, such as quantitative computer tomography (QCT). Therefore, we assessed the feasibility of a more practical and inexpensive approach through application of phalangeal quantitative ultrasound (pQUS; IGEA DBM BP Sonic 1200, Sensweiler, Germany) in a cross-sectional study of 521 men, aged 18–91 years (224 healthy controls, 156 newly diagnosed hypogonadal, and 141 T substituted men). The method was compared with QCT of the lumbar spine in the first 80 patients. We evaluated longitudinal changes of amplitude-dependent speed-of-sound (AdSoS) in 54 hypogonadal men from the beginning of T substitution. AdSoS decreased with age (p < 0.0001) and with declining total T concentration, with a four to fivefold larger reduction in AdSoS for each nanomole-per-liter decrement in total T in the hypogonadal range (<12 nmol/L) compared with the eugonadal range (p < 0.0001). AdSoS was higher in eugonadal and substituted men than in hypogonadal patients (p < 0.0001, by analysis of covariance [ANCOVA]). Substituted men <50 years of age showed lower AdSoS than eugonadal men (p = 0.004) and untreated men with secondary hypogonadism had lower values than men with primary hypogonadism (p = 0.005). Therapeutic effects were seen regardless of age, diagnosis, or T substitution modality. In the longitudinal approach, AdSoS increased from 1986 ± 93 to 2035 ± 77 m/sec over 237 ± 57 days with the highest gain in those men with initially the lowest values (p < 0.0001, by ANCOVA for repeated measurements). In comparison to QCT, patients with a lumbar content of hydroxylapatite of <100 mg/cm3 were reliably identified by pQUS (cutoff level 1965 m/sec, T score −3.5 based on eugonadal subjects; receiver operating characteristics: area under the curve [AUC] 0.94, sensitivity 94.1, specificity 92%, p < 0.0001), but specific values of lumbar BMD could not be predicted by pQUS. pQUS represents a feasible, sensitive, and inexpensive method for assessing bone tissue in hypogonadal men over the full age range and also for monitoring the effects of T substitution. [ABSTRACT FROM AUTHOR]

Recent reports of osteoporosis in congenital estrogen deficiency in humans from estrogen resistance or aromatase deficiency have called attention to the importance of estrogen in males. It is the purpose of the present study to evaluate the effects of low- dose estrogen on glucose, lipid and bone metabolism in males with hypogonadism. Nine Thai males with primary or secondary hypogonadism were included in the study. Testosterone was discontinued at least 8 weeks before the study. The subjects received 0.3 mg of conjugated equine estrogen (CEE) daily for 4 weeks. Serum C-terminal telopeptide of type 1 collagen (CTX), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride (TG) and parameters related to insulin sensitivity were measured at baseline and 4 weeks after treatment. Insulin sensitivity was assessed by frequent intravenous glucose tolerance test. The mean age of subjects was 35.77 years (22–70 years). Insulin sensitivity index (SI) did not change significantly after the administration of CEE (P=0.09). Likewise, no change in acute insulin response (AIRglucose) was detected. However, glucose effectiveness (SG) significantly decreased after CEE (P<0.05). No significant change in serum TC, LDL-C, HDL-C or TG was detected. In regard to bone turnover, serum CTX significantly decreased after CEE administration (P<0.05). We concluded that low-dose estrogen administration in hypogonadal males for 4 weeks causes a decrease in bone turnover and an increase in glucose effectiveness. No effect on serum lipid concentrations or insulin sensitivity and secretion was detected. [Copyright &y& Elsevier]

Summary. Endothelin has various paracrine and endocrine effects on the male reproductive system. Testosterone is probably responsible for the higher endothelin levels in males. In addition, there is much ambiguity about the relationship between gonadotrophic hormones and endothelin. In order to study in more detail the relationship of endothelin with the hypothalamo-pituitary-gonadal axis in the male, we investigated 18 male patients with various forms of hypogonadism (seven with hypergonadotrophic hypogonadism and 11 with hypogonadotrophic hypogonadism). Eight age-matched healthy males served as controls. The basal endothelin levels in patients with hypogonadism (0.95 ± 0.53 fmol ml-1 ) were significantly higher than those of the controls (0.54 ± 0.06 fmol ml-1 ; P < 0.05). Males with hypergonadotrophic hypogonadism had significantly increased endothelin concentrations (1.05 ± 0.57 fmol ml-1 ; P < 0.05), whereas those with hypogonadotrophic hypogonadism (0.89 ± 0.53 fmol ml-1 ) had nonsignificantly (P > 0.05) elevated levels. No significant correlation was found between plasma endothelin levels and gonadotrophin, prolactin and testosterone concentrations. The results of this study suggest that plasma endothelin levels are increased in males with hypogonadism. [ABSTRACT FROM AUTHOR]

Summary. Hypogonadism is one of the crucial risk factors for male osteopenia and osteoporosis. There are few studies on the effects of long-term and consistently administered testosterone substitutive therapy on bone mineral density in men with gonadal androgen deficiency, and their results have been susceptible to various interpretations. The aim of our study was an evaluation of bone mineral content in 26 men, aged 18–57 years, with hypergonadotrophic hypogonadism who underwent long-lasting androgen re-placement therapy with testosterone esters (Omnadren 250), which conditioned proper psychosomatic androgenization. The control group comprised 405 healthy men, aged 20–60 years, a representative sample of the local male population. Among all examined men and in the control group, trabecular, cortical and total bone mineral content at the distal radius of the nondominant hand were assessed by peripheral quantitative computed tomography using the Stratec 960 apparatus. In 11 hypogonadal men (42.3%), the trabecular bone mineral content was found to be within normal ranges; in 15 patients (57.7%) its values were below -1 standard deviation (SD) (osteopenia). In six patients (23.1%), the cortical bone mineral content was between +1 SD and the arithmetic mean, X; in 13 examined men (50%), the cortical bone mineral content was below X and above -1 SD. Osteopenia was diagnosed in six hypogonadal males, whereas osteoporosis was found in one man (cortical bone mineral content below -2.5 SD). Only in seven of the examined men (26.9%) was the total bone mineral content found within normal ranges, whereas in 19 men (73.1%) the total bone mineral content was below -1 SD (osteopenia). Despite the testosterone replacement in hypogonadal men, the greatest reduction of bone mineral content was found in its trabecular and total values. Among all the men examined, the trabecular and total bone mineral contents were below the mean of our own reference values. The... [ABSTRACT FROM AUTHOR]